Our laboratory has shown that several HlV-2 strains replicate well in cultured baboon peripheral blood mononuclear cells (PBMG). The UC2 strain has been inoculated into five baboons (Papio papio sp) leading to persistent infection with lymphadenopathy in all animals and a decline in CD4+ lymphocytes in two animals at about 1.5 years post-infection. Three additional animals showed signs of persistent infection following inoCulation with another HIV-2 strain (UC14). Two of these baboons exhibited plasma viremia, and one of these animals has shown a dramatic loss in CD4+ Cells after only 16 weeks. We wish to develop this animal model to study vaccine approaches for the human immunodeficiency virus (HIV). It could also be helpful in evaluating therapy and viral pathogenesis. To date, no Consistent, reproducible animal model for HIV has been established, and models based on SIV could differ in important ways from those based on human lentivirus counterparts. Moreover, the baboon model could be valuable for understanding and countering an HIV-2 pandemic. A pilot study is proposed to evaluate baboons inoculated with two additional strains of HIV-2 to establish a persistent infection. Animals will be monitored for virus load in PMC, lymph node and other tissues; host immune responses; and clinical signs and symptoms of infection. We will also derive an infectious molecular clone of one other HIV-2 strain besides UC2 that grows well in baboons. Finally, if time permits, a DNA vaccine will be derived from the previously cloned UC2 Env (gp160) and tested in baboons. HIV-2 infection of baboons promises to be an excellent reproducible and economical approach for studying HIV prevention, treatment, and pathogenesis.